Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

Abstract

It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer's kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.

Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies

“…There are scavenger receptors on activated monocytes and macrophages such as LOX-1, which can potentially bind and take up Hsp70 (Delneste et al 2002;Theriault et al 2005). Another possible mechanism might be elimination by naturally occurring anti-Hsp70 antibodies (Molvarec et al 2009a). However, anti-Hsp70 IgG markedly enhanced the capacity of Hsp70 to induce proinflammatory immunity (Yokota et al 2006).…”

Serum level of soluble 70-kD heat shock protein is associated with high mortality in patients with colorectal cancer without distant metastasis

“…The detection range of the assay was 0.05 to 10 ng/ml; intra-/ inter-assay variability was <10%/<16%, respectively. Serum concentration of the IgG type antibodies against HSP70 were determined as described in Molvarec et al (2009).…”

Serum heat shock protein 70 and oxidized LDL in patients with type 2 diabetes: does sex matter?

“…HSPA1A/B (HSP70) is one of the members of the HSP family that have been most extensively studied Hageman and Kampinga 2009). HSP70 expression increases under stressful conditions (Ireland et al 2007;Pandey et al 2009;Soti et al 2005;Tamasi et al 2009;Molvarec et al 2009a) and is positively correlated with markers of inflammation, such as CRP, monocyte count, serum aspartate aminotrasferase, LDH activity, plasma malondialdehyde level and TNF-α (Njemini et al 2004;Mayer and Bukau 2005;Molvarec et al , 2007aMolvarec et al , 2009b. We have previously shown that circulating levels of HSP70 is increased with duration of diabetes and is associated with the chronicity of the disease (Nakhjavani et al 2010).…”